Asymptomatic Aortic Stenosis Patients Research Articles

Natural history of initially asymptomatic severe aortic stenosis: a one-stage meta-analysis.

Current guidelines on the management strategy for patients with asymptomatic severe aortic stenosis (AS) remain unclear. This uncertainty stems from the lack of data regarding the natural history of these patients. To address this gap, we performed a systematic review and meta-analysis examining the natural history of asymptomatic severe AS patients receiving conservative treatment. The PubMed, Cochrane, and Embase databases were searched from inception to 24 January 2024 using the keywords "asymptomatic" AND "aortic" AND "stenosis". We included studies examining patients with asymptomatic severe AS. In interventional trials, only data from conservatively managed arms were collected. A one-stage meta-analysis was conducted using individual patient data reconstructed from published Kaplan-Meier curves. Sensitivity analysis was performed for major adverse cardiovascular outcomes in patients who remained asymptomatic throughout follow-up. A total of 46 studies were included (n = 9545). The median time to the development of symptoms was 1.11years (95% CI 0.90-1.53). 49.36% (40.85-58.59) of patients who were asymptomatic had suffered a major adverse cardiovascular event by 5years. The median event-free time for heart failure hospitalization (HFH) was 5.50years (95% CI 5.14-5.91) with 36.34% (95% CI 33.34-39.41) of patients experiencing an HFH by year 5. By 5years, 79.81% (95% CI 69.26-88.58) of patients developed symptoms (angina, dyspnoea, syncope and others) and 12.36% (95% CI 10.01-15.22) of patients died of cardiovascular causes. For all-cause mortality, the median survival time was 9.15years (95% CI 8.50-9.96) with 39.43% (CI 33.41-36.40) of patients dying by 5years. The median time to AVR was 4.77years (95% CI 4.39-5.17), with 52.64% (95% CI 49.85-55.48) of patients requiring an AVR by 5years. Our results reveal poor cardiovascular outcomes for patients with asymptomatic severe AS on conservative treatment. A significant proportion eventually requires an AVR. Further research is needed to determine if early intervention with AVR is more effective than conservative treatment.

Design and rationale of the evaluation of transcatheter aortic valve replacement compared to surveillance for patients with asymptomatic severe aortic stenosis: The EARLY TAVR trial

For patients with asymptomatic, severe aortic stenosis (AS) and preserved left ventricular ejection fraction, current guidelines recommend clinical surveillance every 6 to 12 months. To date, no randomized trials have examined whether an early intervention with transcatheter aortic valve replacement (TAVR) will improve outcomes among these patients. EARLY TAVR is a prospective, randomized, controlled, and multicenter trial, with an event-based design. Asymptomatic severe AS patients (n=900) are randomized 1:1 to either clinical surveillance or TAVR with the Edwards SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve. Patients are stratified by whether they are able to perform a treadmill stress test. The primary end point is death, stroke, or unplanned cardiovascular hospitalization. Patients who are asymptomatic but have a positive stress test will be followed in a registry and undergo aortic valve replacement as per current guidelines. EARLY TAVR is the largest randomized trial to date assessing the role of early intervention among patients with asymptomatic severe AS compared to clinical surveillance and the first to study the role of TAVR. NCT03042104.

Novel Biomarkers and Advanced Cardiac Imaging in Aortic Stenosis: Old and New.

Currently, the symptomatic status and left ventricular ejection fraction (LVEF) play a crucial role in aortic stenosis (AS) assessment. However, the symptoms are often subjective, and LVEF is not a sensitive marker of left ventricle (LV) decompensation. Over the past years, the cardiac structure and function research on AS has increased due to advanced imaging modalities and potential therapies. New imaging parameters emerged as predictors of disease progression in AS. LV global longitudinal strain has proved useful for risk stratification in asymptomatic severe AS patients with preserved LVEF. The assessment of myocardial fibrosis by cardiac magnetic resonance is the most studied application and offers prognostic information on AS. Moreover, the usage of biomarkers in AS as objective measures of LV decompensation has recently gained more interest. The present review focuses on the transition from compensatory LV hypertrophy (H) to LV dysfunction and the biomarkers associated with myocardial wall stress, fibrosis, and myocyte death. Moreover, we discuss the potential impact of non-invasive imaging parameters for optimizing the timing of aortic valve replacement and provide insight into novel biomarkers for possible prognostic use in AS. However, data from randomized clinical trials are necessary to define their utility in daily practice.

Abstract 15422: Diffuse Myocardial Fibrosis Predicts Outcome in Moderate and Asymptomatic Severe Aortic Stenosis

Introduction: Patients with moderate or asymptomatic severe aortic stenosis (AS) are at increased risk of cardiovascular events, but markers to guide intervention are lacking. We investigated the use of cardiovascular magnetic resonance (CMR) to identify drivers of outcome. Methods: Moderate (aortic valve area [AVA] 1.0-1.5 cm2) or asymptomatic severe AS patients (AVA≤1.0 cm2 and NYHA functional class I-II) (n=457) were prospectively enrolled from five international sites and parameters including extracellular volume fraction (ECV%) and late gadolinium enhancement were analyzed on CMR. Clinical events were defined as all-cause mortality and admission for heart failure. Results: Moderate AS patients had smaller left ventricular (LV) mass and less diastolic dysfunction compared to asymptomatic severe AS patients, but showed no difference in the extent of myocardial fibrosis and scar. During median 5.7-years follow-up, 83 clinical events occurred. Patients with clinical events had smaller AVA, greater diastolic dysfunction, and higher ECV% (median [interquartile range] ECV% 26.3% [24.3-29.8] vs 28.2% [25.5-30.8], P=0.003). There was a stepwise increase of clinical events across ECV tertiles. ECV% was associated with clinical outcome (adjusted HR 1.05, 95% CI 1.00–1.09, P=0.035), independent of AVA and aortic valve replacement as a time-dependent covariate. The prognostic significance of ECV% was consistent when AS severity was alternatively defined using aortic peak velocity and mean pressure gradient, and also across subgroups by AS severity and symptoms, AVA, aortic peak velocity, mean pressure gradient, and left ventricular ejection fraction (Figure). Conclusions: Increased diffuse myocardial fibrosis is associated with poor outcomes in moderate and asymptomatic severe AS patients and can help identify those who require closer surveillance and possibly earlier intervention.

Abstract 17617: Toward Improving Diagnosis and Interventional Predictability in Aortic Valve Stenosis Using Computational Modeling

Introduction: Watchful waiting for symptoms or critical hemodynamics to intervene on aortic stenosis (AS) may delay too long. While stress tests can detect symptoms in allegedly asymptomatic AS patients, image-based computations based on advanced modeling techniques can provide critical biomechanical insights. Hypothesis: Advanced computational modeling techniques utilizing patient data backed by high-performance computing can inform a personalized understanding of disease progression, diagnosis, and anticipated post-op hemodynamics to predict interventional efficacy. Methods: A validated in-house Fluid-structure Interaction (FSI) algorithm that allows easy translation of patient-specific anatomies was utilized to perform "virtual stress test" on a moderate AS with increasing LV contraction to predict systolic ejection dynamics under stress. TAVR was virtually implanted and post-op aortic hemodynamics were quantitatively compared with pre-op (diseased) data. Results: Predictions demonstrated that that aortic flow turbulence in moderate AS (Re = 11,700) during exercise (115 bpm) can be similar to severe AS (Re=10,000) at rest (70 bpm) resulting in a greater dissipation losses rising linearly with heart rates. As LV contraction rose, each valve cusp underwent a distinct non-linear rise (>100%) in mechanical stresses that can accelerate calcification. Interestingly, our evaluation revealed that the heterogenous ΔP vs. Q relationship in AS observed clinically can be attributed to a non-linear rise in aortic valve area occurring during mid-systole. Aortic hemodynamics improved post-TAVR by reducing dissipation losses by ~11 fold and restoring near-normal peak-systolic velocity (1.7 m/s) in the ascending aorta. Conclusions: High-performance based multi-physics algorithms incorporating patient data might offer comprehensive biomechanical insights into diagnosis and interventional suitability for aortic valve stenosis.

Supine ergometry induced changes of left ventricular function and pulmonary hypertension have an uneven prognostic relevance for asymptomatic aortic stenosis according to age and gender

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Risk stratification in the asymptomatic severe aortic stenosis (AS) remains a difficult task within the spectrum of its hemodynamic phenotypes, especially on aging demographics. Interplay of left ventricular function and AS hemodynamics may be studied using semisupine bicycle ergometry (SBE). Purpose Purpose of the study was to interrogate the prognostic relevance of SBE based evaluation of LV function and noninvasive hemodynamics in asymptomatic severe AS. Methods Seventy-eight asymptomatic severe AS patients (pts), followed up on valve clinic in a tertiary center (age 65±12 years, female 29), were referred for SBE. AS related cardiac events (independent decision for surgery, NYHA worsening) during a follow up of 33/21 months occurred in 25 pts (64% for age>65 vs 30% for age<65). Workload (Watts) and % achieved target heart rate (%targetHR) were considered surrogates for SBE efficiency. The following parameters (mean±SD) were estimated at rest(R) and SBE (Ex): Biplane LV ejection fraction (EF) and stroke volume (SV), 2D strain (SR), tricuspid peak gradient (TRPG), transmitral E/e, HR, systolic blood pressure (SBP), HR*SBP product and their respective % changes. Results Event group had a decreased SBE efficiency in workload (Watts: 59±16 vs 78±20, p<0.001), similar %target heart rate (73±13 vs 73±9), with differences among the continuous variables only in EFex (59±8 vs 63±7, p = 0.04) and %dLVEF (6±10 vs 12±10, p = 0.02). Categorical classification was performed for inadequate LV functional improvement at SBE, using the absolute cut off for <5% LVEF increase and the <3% for LVSR increase, as well as for an excessive increase in pulmonary hypertension at SBE, using the cut off for TRPG >55mmHg. Respective distribution of cases was similar for age category > or <=65 years (dEX <5: 46% vs 45%, dSR <3: 62% vs 87%, TRPGEx >55mmHg: 38% vs 48%, all p = ns). Kaplan Meier analysis for events using TRPG>55 was significant for females (log rank=3.2, p = 0.06/ figure1). Kaplan Meier analysis for events using dEF≥5 was significant for age <65 years (log rank =4.7, p = 0.03/figure2). LVSR cut off did not provide any difference in outcome. Conclusion SBE induced changes on LV function and pulmonary hypertension have an uneven risk stratification relevance according to age and gender. Dedicated algorithms to gender and age have to be applied for the improvement of prognostication in severe AS based on SBE.

Abstract 10747: Left Atrial Volume Index is Associated With New-Onset Heart Failure Admission and Cardiovascular Death in Patients With Asymptomatic Moderate Aortic Stenosis

Background: Left atrium enlargement is the marker of increased left ventricular (LV) filling pressure and morphological indicator of chronically increased hemodynamic burden. However, the potential utility and clinical significance of left atrial volume (LAV) index in asymptomatic moderate aortic stenosis (AS) patients have been unknown. Therefore, we assessed the impact of LAV index on cardiovascular events in asymptomatic moderate AS patients. Methods: We retrospectively analyzed 549 patients (mean age 79±13 years) with asymptomatic moderate AS (mean transaortic pressure gradient 20 to 39 mmHg) and LVEF ≥50 %. Cardiovascular events were defined as cardiovascular death or admission for heart failure (HF). Results: During a follow-up period (median, 1301 days; range, 296 to 2179 days), 216 patients underwent aortic valve replacement (AVR) or balloon aortic valvuloplasty (BAV), and 132 HF admission and 37 cardiovascular deaths occurred. In the multivariable analysis, LAV index, lateral E/e′, and peak tricuspid regurgitation velocity were independent predictors of cardiovascular events (Hazard ratio (HR) 1.07 [1.05 to 1.09]; HR 1.04 [1.00 to 1,08]; HR 1.04 [1.00 to 1.07], respectively) after adjusting for age, female, body mass index, previous myocardial infarction, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, moderate mitral regurgitation, E velocity, LV hypertrophy, and surgical or transcatheter AVR or BAV. LAV index of 27 mL/m 2 was the optimal cutoff value for predicting cardiovascular events with sensitivity of 89% and specificity of 60% and C-statistics for LAV index demonstrated superiority to lateral E/e′ and peak tricuspid regurgitation velocity ( P <0.001) (Figure). Conclusion: LAV index is an important predictor for cardiovascular events in asymptomatic moderate AS patients.

Abstract 15210: Association of Circulating Biomarkers With Progressive Left Ventricular Remodeling and Hypertrophy in Patients With Aortic Stenosis: Results From the Progressa Study

Introduction: Aortic stenosis (AS) is associated with progressive left ventricular (LV) remodeling and hypertrophy, ultimately leading to cardiac decompensation. Measurement of circulating biomarkers may be useful to identify AS patients with higher risk of maladaptive LV remodeling, a potent marker of the transition to heart failure. We hypothesized that multiple circulating biomarkers are associated with faster progression of LV hypertrophy in patients with AS. Methods: One hundred and forty-six asymptomatic AS patients (66±13years, 75% male) prospectively enrolled in the PROGRESSA study (NCT01679431) were included in this sub-analysis. All patients underwent Doppler-echocardiography to measure AS severity, LV mass indexed to body surface area (LVMi) and LV relative wall thickness (RWT). The annualized changes in LVMi and RWT were calculated between baseline and last follow-up visit (mean follow-up of 2.5±1.88 years). Results: At baseline, 16% of patients had mild (i.e. peak aortic jet velocity [Vpeak] 2.0-2.9 m/s),76% moderate (Vpeak 3.0-3.9 m/s), and 8% severe (Vpeak ≥4.0 m/s) AS, mean LVMi and RWT were 106±23 g/m 2 and 0.47±0.07 respectively. Among biomarkers, baseline level of triglycerides, D-dimer and tumor antigen 125(Ca-125) were significantly associated with LVMi progression rate (β:0.16,p≤0.05), (β:0.18,p≤0.05) and(β:-0.20,p≤0.05) respectively. Soluble (ST2) protein and alkaline phosphatase (ALP) were the only factors independently associated with the annualized change in RWT. In multivariate analysis adjusted for age, gender, comorbidities, AS severity, cardiac biomarkers; triglycerides and D-dimers remained significantly associated with faster progression rate of LVMi (all, p≤0.05), while lower level of CA125 remained significantly associated with LVMi annualized change (β=-0.21, p=0.01). After similar multivariate adjustment, higher levels of ST2 and ALP remained significantly associated with faster progression rate of RWT (all, p≤0.05). Conclusion: Several blood biomarkers were independently associated with faster progression of LV remodeling and hypertrophy in patients with AS. A multiple biomarker approach may be useful to assess LV health and predict the risk of early phases of heart failure in AS.

Abstract 11191: Early Surgery versus Conservative Management Among Patients With Asymptomatic Aortic Stenosis: A Meta-Analysis

Introduction: With the increasing prevalence of asymptomatic severe AS and its progression to the symptomatic stage the early surgical aortic valve repair is emerging as a popular option but with limited evidence of its efficacy and safety. Objective: We aimed to conduct a meta-analysis to evaluate the efficacy and safety to early surgical aortic valve repair as compared to conservative management. Methods: A systematic literature search was performed in PubMed, Scopus, Embase and Cochrane databases for studies comparing the early surgery versus conservative management among asymptomatic aortic stenosis patients. The primary outcome was all-cause mortality. Secondary endpoints were cardiovascular mortality (CVM), sudden cardiac death (SCD), hospitalisation due to heart failure, the composite of mortality and MACCE, Clinical thromboembolic events, major bleeding, myocardial infarction (MI), and stroke. Results: A total of 5 articles (3 observational studies and 2 randomized controlled trials) were included. We found that there were significantly lower odds of all-cause mortality [OR, 0.33; (95%CI:0.25-0.42); p<0.000001], cardiovascular mortality [OR, 0.34 (95%CI:0.25-0.47); p<0.00001] and composite of mortality and MACE (OR:0.32(95%CI:0.24,0.42;p<0.00001), sudden cardiac death (OR:0.32; CI: 0.16-0.64; p=0.001) and hospitalization due to heart failure (OR:0.27, CI: 0.16-0.44; p<0.00001) with early surgical aortic valve repair compared to conservative management. There was no significant difference between the incidence of major bleeding, clinical thromboembolic events, stroke and myocardial infarction between the conservative care groups and early surgery. We also found a reduced risk of Conclusion: Among asymptomatic patients with AS, SAVR shows better outcomes in reducing mortality and other complications compared with the conservative management approach.

Abstract 14070: Role of Early Aortic Valve Replacement versus Conventional Management in Asymptomatic Patients With Severe Aortic Stenosis: A Meta-Analysis

Introduction: Aortic-valve replacement (AVR) is an effective therapy for patients with severe symptomatic aortic stenosis (AS) but the appropriate timing of intervention for asymptomatic patients with severe AS remains controversial. Increased mortality associated with the onset of symptoms challenges the conventional “watchful waiting” strategy followed for this subset of patients. An early intervention may be warranted, however the data supporting this hypothesis is small. Our aim was to perform meta-analysis looking at outcomes of early surgical AVR (SAVR) in asymptomatic severe AS patients with preserved LVEF. Methods: Electronic databases were searched for studies comparing early SAVR and conventional treatment in patients with asymptomatic severe AS and normal LV function. The primary outcome of interest was all cause mortality. Secondary outcome was heart failure hospitalization. Random-effects model was used to estimate the pooled risk ratio (RR), and 95% confidence interval (CI) using Revman 5.4.1. Subgroup analysis stratified by study design was performed. Heterogeneity was assessed by Higgins I 2 statistic. Results: We found total of 8 studies (2 RCTs; 6 observational) from which 2669 patients with asymptomatic severe AS were identified. 1354 underwent SAVR and 1315 were managed conservatively. The mean age was 68 years with mean follow up duration of 4.8±2 years. There was statistically significant reduction in all-cause mortality (RR: 0.37; CI: 0.27-0.50; p<0.05; I2 = 68%) and heart failure hospitalization (RR: 0.24; CI: 0.16-0.36; p<0.05; I2 = 0%) among patients who underwent AVR compared with conservative treatment with subgroup analysis by study design showing similar trends. Conclusion: Our meta-analysis shows that compared with conventional treatment strategy, early SAVR in asymptomatic patients with severe AS is associated with improved long-term outcomes notably reduced all cause mortality and heart failure hospitalizations.

Value of cardiopulmonary exercise test submaximal parameters in the assessment of aortic stenosis patients

Abstract Background Exercise test is recommended for risk stratification of asymptomatic patients with severe aortic stenosis (AS), although a significant number of patients can't perform a maximal exercise test, increasing the potential value of sub-maximal parameters for the assessment of these patients. Aim To assess which parameters could be useful for risk stratification in case of a submaximal Cardiopulmonary Exercise Testing (CPET) in asymptomatic patients with severe AS. Methods Retrospective evaluation of adult patients with asymptomatic severe AS, in a single center, who underwent CPET between December 2016 and November 2021. All patients underwent a treadmill CPET using an exercise protocol with progressive increase in workload. Patients were divided in group A (maximal CPET) or group B, respectively, if respiratory exchange ratio (RER) was >1.10 at peak exercise or below this value. Known parameters accessed in a submaximal CPET were evaluated: mean minute ventilation/carbon dioxide production slope (VE/VCO2), VO2 value in first ventilatory threshold (VT1), peak circulatory power, and oxygen uptake efficiency slope (OUES). Results CPET was performed in 25 patients with severe asymptomatic AS (80 years ± 7 years, 56% male), median AVA was 0.86 cm2 [IQR 0.65–0.95 cm2] and transaortic pressure gradient was 46 mmHg [IQR 41–55 mmHg]. The most used protocol was a ramp slope. Nineteen patients (76%) didn't reach a RER>1.10 (group B) due to respiratory (26%) or peripheral limitation (53%). Comparing both groups, group B patients showed a shorter duration of exercise of (8±3 min vs. 9±4 min, p=0.422), and a lowest mean peak VO2 (16.3±3.6 vs. 20.5±6.9 ml/kg/min, p=0.207). In our population, bivariate analyses demonstrated that OUES was the only submaximal parameter that could discriminate both groups: Group B patients had the lowest values (1.53 [IQR 1.47–1.70] vs. 1.94 [IQR 1.56–2.11], p=0.042). ROC curve analysis of OUES values revealed an AUC of 0.78 (p=0.042) for maximal CPET prediction. The cut-off point with most sensitivity (S) and specificity (E) obtained using the Youden index (0.62) was 1.9 (S≈67%; E≈95%) (Figure 1). Conclusions In our cohort of asymptomatic AS patients, even with submaximal CPET, OUES accurately identify patients with higher degrees of functional limitation. Whether OUES is useful as prognostic marker to the workflow treatment of AS it's worth to be assessed prospectively. Funding Acknowledgement Type of funding sources: None.

The Role of Transcatheter Aortic Valve Replacement in Asymptomatic Aortic Stenosis: A Feasibility Analysis.

Surgical aortic valve replacement (SAVR) is the current treatment of choice for good surgical candidates with moderate to severe symptomatic aortic stenosis (AS). As transcatheter aortic valvular replacement (TAVR) has shown an improved one and two-year all-cause mortality, it has been chosen for moderately symptomatic severe AS patients. The purpose of this review was to perform a clinical comparison of TAVR vs. SAVR and to analyze the Health Index Factor (HIF) that makes TAVR a treatment of choice in asymptomatic AS patients. An extensive literature search of PubMed, Cochrane, and Embase databases was performed using the keywords “Aortic stenosis”, “SAVR”, “TAVR”, and “Asymptomatic”. A total of 45 prospective randomized clinical trials in the English language that were published from the year 2000 onwards were included in the final analysis. It has been found that 59.3% of asymptomatic AS patients are likely to die in the next five years without proactive treatment. Multiple studies have proven that early intervention with aortic valve replacement is superior to conservative treatment in severe asymptomatic AS; however, the choice between SAVR and TAVR is not well established. The NOTION Trial, SURTAVI Trail, and PARTNER 3 study have shown the non-inferiority of TAVR over SAVR, during one-year follow-up for low surgical risk patients. Evolut Low-Risk study and Early TAVR are the only two prospective studies performed to date that have enrolled patients with asymptomatic severe AS. The Evolut Trial demonstrated no difference in all-cause mortality at 30 days (1.3% vs. 4.8%. p=0.23), and 12 days (1.3% vs. 6.5%, p=0.11). Additionally, TAVR also decreases the risk of post-procedural atrial fibrillation, acute kidney injury (AKI), and rehospitalization, and leads to significant improvement in the mean trans-aortic pressure gradient. TAVR also showed marked improvement in the 30-day Quality of Life (QOL) index, where SAVR did not report any significant change in the QOL index. However, the official recommendations of Early TAVR are still awaited. TAVR has consistently shown a statistically non-significant difference in case mortality, risk of stroke, and rehospitalization with moderate to high surgical risk patients whereby recent initial trials have shown significant improvement in the QOL index and hemodynamic index for patients with asymptomatic disease. More extensive studies are required to prove the risk stratifications, long-term outcomes, and clinical characteristics that would make TAVR a preferred intervention in asymptomatic patients.

Early surgery vs conservative management among asymptomatic aortic stenosis: A systematic review and meta-analysis.

Although aortic valve replacement in severe symptomatic Aortic Stenosis (AS) are clearly outlined, the role of surgical intervention in asymptomatic severe AS remains unclear with limited evidence. The aim of our meta-analysis is to evaluate the efficacy and safety of early surgical aortic valve repair compared to conservative management. A systematic literature search was performed in PubMed, Scopus, Embase and Cochrane databases for studies comparing the early surgery versus conservative management among asymptomatic aortic stenosis patients. Unadjusted odds ratios (OR) were pooled using a random-effect model, and a p-value of<0.05 was considered statistically significant. A total of 5 articles (3 observational studies and 2 randomized controlled trials) were included. At a median followup of 4.1years, here were significantly lower odds of all-cause mortality [OR=0.30 (95%CI:0.17-0.53), p<0.0001], cardiovascular mortality [OR=0.35 (95%CI:(0.17-0.72), p=0.005], and sudden cardiac death (OR=0.36 (95%CI: 0.15-0.89), p=0.03) among early surgery group compared with conservative care. There was no significant difference between incidence of major bleeding, clinical thromboembolic events, hospitalization due to heart failure, stroke and myocardial infarction between the conservative care groups and early surgery. Among asymptomatic patients with AS, early surgery shows better outcomes in reducing all-cause mortality and cardiovascular mortality compared with conservative management approaches.

Antihypertensive treatment and risk factors for syncope in asymptomatic aortic stenosis patients with hypertension

ABSTRACT Background Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis(AS) is scarce. Objectives Given the paucity of data on the relationship between syncope and antihypertensive treatment in aortic stenosis. This study sought to investigate this association in patients admitted to our hospital. Methods A total of 158 patients with asymptomatic moderate or severe aortic stenosis were analyzed. Follow-up was conducted by clinic visit, telephone contact, or review of electronic medical records. Outcomes were syncope. Results Hypertension were documented in 90 of the 158 patients with moderate or severe AS, and 77 of them received antihypertensive medications. During an average 28 months follow-up period, the occurrence of syncope was observed in 13 patients. Among them, 8 were in antihypertensive group (n = 77) and 5 in normotensive group (n = 68). There was no significant difference in incidence of syncope between the two groups. Patients with treated hypertension and syncope had a lower stroke volume index (SVi), a higher valve arterial impedance (ZVA), a smaller SAC than those without. Kaplan-Meier analysis showed that there was no significant difference in syncope cumulative incidence between antihypertensive group and normotensive group (log rank P = .478). Multivariate cox regression analysis showed that both ZVA (hazard ratio:19.006, 95% confidence interval: 4.664 to77.448;P = .002) and LVMI (hazard ratio:1.484, 95% confidence interval: 1.427 to 5.157;P = .016) were associated with development of syncope, whereas hypertension were not related independently to syncope (hazard ratio:0.935, 95% confidence interval: 0.786 to3.173; P = .869). Conclusions In patients with moderate or severe AS, concomitant hypertension, and antihypertensive treatment didn’t increase the occurrence of syncope, whereas higher ZVA was independently associated with greater risk of syncope.

Abstract 9493: Differences in Prognostic Implications of Changes in Echocardiography in Asymptomatic Severe Aortic Stenosis Managed Conservatively

Background: No previous study has explored the association between the changes in echocardiographic parameters during follow-up and clinical outcomes in patients with asymptomatic severe aortic stenosis (AS) and who were managed conservatively. Objective: This study aimed to investigate the prognostic impact of the changes in echocardiographic parameter at 1-year follow-up in asymptomatic severe AS patients managed conservatively. Methods: Among 3815 patients with severe AS enrolled in the multicenter CURRENT AS registry in Japan, we analyzed conservatively managed 555 patients who underwent echocardiography at 1-year follow-up and remained asymptomatic. The primary outcome measure was a composite of AS-related deaths and hospitalization due to heart failure. A decline in left ventricular ejection fraction (LVEF), an increase in left ventricular end-diastolic dimension (LVEDD), and an increase in aortic valve pressure gradient (PG) were defined as above 10%, 5mm, and 30mmHg, respectively, based on the clinically relevant values. Results: There were 61 patients (11.0 %) with &gt;10% decline in LVEF and 494 patients (89.0%) without decline. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the decline in LVEF group than in no decline in LVEF group. After adjusting for confounders, the excess risk of the decline in LVEF relative to no decline in LVEF for the primary outcome measure remained significant (hazard ratio; 2.76, 95% confidence interval 1.66-4.45). The cumulative 3-year incidence of the primary outcome measure was significantly higher in the increase in LVEDD group than in no increase in LVEDD group. In contrast, there were no difference in cumulative 3-year incidence of the primary outcome measure between the increase in aortic valve PG and no increase group. Conclusions: Severe asymptomatic AS patients with a &gt;10% LVEF decline or &gt;5mm increase in LVEDD at 1-year after diagnosis had worse AS-related clinical outcome than those without under conservative management, whereas there were no differences in the outcomes stratified by changes in aortic valve PG. This indicated the importance in the LV morphology and function during follow-up in asymptomatic severe AS patients when managed conservatively.

Left atrial dynamics in the hemodynamic response during exercise in patients with asymptomatic severe aortic stenosis

Abstract Background The hemodynamic impact of left atrial (LA) dynamics in aortic stenosis (AS) in relation to cardiopulmonary response to exercise has never been studied. We aimed at investigating the link between LA function vs hemodynamics and prognosis in asymptomatic severe AS patients. Methods A total of 106 patients: 76 asymptomatic severe AS patients (aortic valve area (AVA) &amp;lt;1.0 cm2 or AVA index &amp;lt;0.6 cm2/m2) and 30 gender-matched control subjects underwent cardiopulmonary exercise testing combined with Echo-Doppler with assessment of LA strain. AS patients were divided into 4 groups according to peak aortic jet velocity (PV), mean pressure gradient (MPG), stroke volume index (SVI), and left ventricular ejection fraction (LVEF). Results Normal-flow low-gradient AS (NFLG: PV &amp;lt;4 m/s and MPG &amp;lt;40 mmHg, SVI &amp;gt;35ml/m2, LVEF ≥50%, N=23), High-gradient AS (HG: PV ≥4 m/s or MPG ≥40 mmHg, LVEF ≥50%, N=23), Paradoxical low-flow low-gradient AS (PLFLG: PV &amp;lt;4 m/s and MPG &amp;lt;40 mmHg, SVI ≤35ml/m2, LVEF ≥50%, N=18), and Classical low-flow AS (CLF: LVEF &amp;lt;50%, N=12) had a higher LA volume index than Control (Control 22±6, NFLG 38±12*, HG 33±9*, PLFLG 33±11*, and CLF 49±15* ml/m2, *P&amp;lt;0.05 vs Control). In PLFLG and NFLG AS, LA strain at rest (21±9 and 26±13%) and during exercise (26±12 and 31±14%) were decreased compared to Control (37±8% at rest, 43±11% during exercise) but LA strain was increased from rest to exercise (P&amp;lt;0.001). HG and CLF AS had no increase in LA strain (31±15 and 19±10% at rest, 28±15 and 18±9% during exercise) (figure). In Cox proportional hazards analysis, age and gender adjusted hazard ratio for the composite end point (aortic valve replacement, hospitalization for heart failure, and all-cause mortality) of changes in LA-strain from rest to exercise (1% increase) was 1.05 (95% CI 1.00 to 1.09, P=0.044) among AS patients. Conclusions In asymptomatic severe AS, the study of LA functional adaptation to exercise plays a key role in the hemodynamic unfavorable cascade signaling major adaptive differences in dynamics during physical challenge. Overall, LA dynamics provides prognostic information also in AS patients. Funding Acknowledgement Type of funding sources: None.

Asymptomatic Patients with Severe Aortic Stenosis and the Impact of Intervention.

Objectives the exact timing of aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS) remains a matter of debate. Therefore, we described the natural history of asymptomatic patients with severe AS, and the effect of AVR on long-term survival. Methods: Asymptomatic patients who were found to have severe AS between June 2006 and May 2009 were included. Severe aortic stenosis was defined as peak aortic jet velocity Vmax ≥ 4.0 m/s or aortic valve area (AVA) ≤ 1 cm2. Development of symptoms, the incidence of AVR, and all-cause mortality were assessed. Results: A total of 59 asymptomatic patients with severe AS were followed, with a mean follow-up of 8.9 ± 0.4 years. A total of 51 (86.4%) patients developed AS related symptoms, and subsequently 46 patients underwent AVR. The mean 1-year, 2-year, 5-year, and 10-year overall survival rates were higher in patients receiving AVR compared to those who did not undergo AVR during follow-up (100%, 93.5%, 89.1%, and 69.4%, versus 92.3%, 84.6%, 65.8%, and 28.2%, respectively; p < 0.001). Asymptomatic patients with severe AS receiving AVR during follow-up showed an incremental benefit in survival of up to 31.9 months compared to conservatively managed patients (p = 0.002). Conclusions: The majority of asymptomatic patients turn symptomatic during follow-up. AVR during follow-up is associated with better survival in asymptomatic severe AS patients.

Electrocardiogram screening for aortic valve stenosis using artificial intelligence.

Early detection of aortic stenosis (AS) is becoming increasingly important with a better outcome after aortic valve replacement in asymptomatic severe AS patients and a poor outcome in moderate AS. We aimed to develop artificial intelligence-enabled electrocardiogram (AI-ECG) using a convolutional neural network to identify patients with moderate to severe AS. Between 1989 and 2019, 258 607 adults [mean age 63 ± 16.3 years; women 122 790 (48%)] with an echocardiography and an ECG performed within 180 days were identified from the Mayo Clinic database. Moderate to severe AS by echocardiography was present in 9723 (3.7%) patients. Artificial intelligence training was performed in 129 788 (50%), validation in 25 893 (10%), and testing in 102 926 (40%) randomly selected subjects. In the test group, the AI-ECG labelled 3833 (3.7%) patients as positive with the area under the curve (AUC) of 0.85. The sensitivity, specificity, and accuracy were 78%, 74%, and 74%, respectively. The sensitivity increased and the specificity decreased as age increased. Women had lower sensitivity but higher specificity compared with men at any age groups. The model performance increased when age and sex were added to the model (AUC 0.87), which further increased to 0.90 in patients without hypertension. Patients with false-positive AI-ECGs had twice the risk for developing moderate or severe AS in 15 years compared with true negative AI-ECGs (hazard ratio 2.18, 95% confidence interval 1.90-2.50). An AI-ECG can identify patients with moderate or severe AS and may serve as a powerful screening tool for AS in the community.

Abstract 15686: Early Intervention versus Conservative Management for Asymptomatic Severe Aortic Stenosis: An Updated Systematic Review and Meta-analysis

Introduction: The management of asymptomatic severe aortic stenosis (AS) is controversial and guidelines for the management of the same is not updated based on recently available evidence. Hypothesis: The main objective is to determine the optimal strategy for the management of asymptomatic severe AS between early intervention versus conservative management. Methods: We performed a systematic electronic search of the PubMed and Cochrane databases from the inception of the database to May 31 st , 2020. We used the Mantel Haenszel method with the Paule-Mandel estimator of Tau 2 and Hartung-Knapp adjustment to calculate relative risk (RR) with a 95% confidence interval (CI) and 95% prediction interval (PI). We used P curve analysis to assess publication bias and estimate the true effect of an intervention. All analysis was carried out using R version 3.6.2. Results: A total of seven studies were included in the final analysis, consisting of 1213 patients with early intervention and 2601 patients with conservative management. Early intervention as compared to conservative management was associated with reduced risk of all-cause mortality (RR: 0.32, 95% CI: 0.21-0.48) (Panel A) , cardiac mortality (RR: 0.36, 95% CI: 0.27-0.48) (Panel B) and non-cardiac mortality (RR: 0.40, 95% CI: 0.28-0.56) (Panel C) . There was no difference in the risk of sudden cardiac death (RR: 0.46, 95% CI: 0.15-1.40), stroke (RR: 0.79, 95% CI: 0.17-3.64), myocardial infarction (RR: 0.44, 95% CI: 0.01-16.82) or heart failure hospitalization (RR: 0.18, 95% CI: 0.01-5.29) between the groups. The pooled estimate for all the outcomes was associated with low-moderate heterogeneity. Conclusions: Among asymptomatic severe AS patients, early intervention is associated with reduced mortality without increasing any procedure-related clinical outcomes. Hence, this meta-analysis supports early intervention as opposed to watchful waiting for the management of asymptomatic severe AS.

High-sensitive Troponin T in asymptomatic aortic stenosis

Abstract Background High-sensitive cardiac Troponin T (hsTnT) is the most frequently used biomarker for the detection of cardiomyocyte injury. Severe aortic stenosis (AS) leads to an increased left ventricular load, with the potential of myocardial injury reflected by increased TnT levels. However, there is a lack of studies showing the prevalence and prognostic role of elevated hsTnT in patients with asymptomatic AS. Purpose To examine the association between the hsTnT levels and AS severity in asymptomatic AS patients. We hypothesized that patients with more severe AS will have elevated hsTnT levels and that hsTnT levels are associated with a higher risk for aortic valve events (AVE) and all-cause mortality (ACM). Methods We performed a post-hoc analysis in 1739 asymptomatic patients with mild to moderate-severe AS, enrolled in the randomized, double-blinded SEAS-study (Simvastatin and Ezetimibe in Aortic Stenosis). All patients had available hsTnT blood samples measured at baseline (Year 0) and Year 1. We defined moderate to severe (mod-severe) AS as a transaortic maximal outflow velocity (Vmax)&amp;gt;3.5 m/s combined with aortic valve area (AVA)&amp;lt;1.0 cm2, otherwise non-severe AS. An hsTnT&amp;gt;14 ng/L was high according to assay (Roche, Elecsys Troponin T hs on cobas e 601). Linear multivariable regression model examined the association of hsTnT levels to clinical and echocardiographic variables. Cox multivariable regression model evaluated competing risks and hazard ratios (HR) of outcomes while adjusting for relevant variables, including a Framingham 10-years risk score of cardiovascular diseases. The competing risks were either ACM or AVE, i.e. the first of AVR, cardiovascular death and heart failure due to AS progression. Results At baseline, hsTnT was high in 26% (453/1739) patients; 25% (380/1529) in non-severe and 35% (73/210) in mod-severe AS. Relative TnT change over one year was 17% (mean 1.17, SD 1.01); 15% in non-severe vs. 32% in mod-severe AS, and neither associated to AS severity, hsTnT at baseline or lipid-lowering treatment. In multivariable linear regression analysis, there were significant correlations between hsTnT at baseline and age, male gender, creatinine, left ventricular mass index and BMI (all p&amp;lt;0.001, R-square=0.42), but not with AS severity. In multivariable Cox regression analyses, a high hsTnT at baseline was associated with AVE 1.61 [95% CI 1.29–1.99]. In contrast, hsTnT at baseline was not associated to all-cause mortality (see figure). Conclusions In asymptomatic AS patients without severe AS, high-sensitive Troponin T is not associated with AS severity in cross-sectional analyses, and its levels do not change substantially during one year of follow-up. However, patients with hsTnT &amp;gt;14 ng/l had a sixty percent higher independent risk of subsequent aortic valve events. Multivariable Cox regression Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Acknowledgements: Main sponsor (SEAS): MSD Singapore Company, LLC, partnership between Merck &amp; Co. Inc. and Schering-Plough Corporation. Blood analysis sponsor: Roche